Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes

Abstract

Neural precursor cells of the ventricular zone give rise to all neurons and glia of the central nervous system and rely for maintenance of their precursor characteristics on the closely related SoxB1 transcription factors Sox1, Sox2 and Sox3. We show in mouse spinal cord that, whereas SoxB1 proteins are usually downregulated upon neuronal specification, they continue to be expressed in glial precursors. In the oligodendrocyte lineage, Sox2 and Sox3 remain present into the early phases of terminal differentiation. Surprisingly, their deletion does not alter precursor characteristics but interferes with proper differentiation. Although a direct influence on myelin gene expression may be part of their function, we provide evidence for another mode of action. SoxB1 proteins promote oligodendrocyte differentiation in part by negatively controlling miR145 and thereby preventing this microRNA from inhibiting several pro-differentiation factors. This study presents one of the few cases in which SoxB1 proteins, including the stem cell factor Sox2, are associated with differentiation rather than precursor functions.

Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei

“…The Sox14-and FoxP1-negative Sox2 + cells turned out to be Olig2 + (Fig. 5J-L), indicating a glial identity (Hoffmann et al, 2014). Furthermore, the expression of Sox14, FoxP1 and Sox2 colocalized with Gbx2…”

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord

“…1B-C‴; supplementary material Fig. S1A-D,F-I,K-N), which at these stages is expressed in glial progenitor and precursor cells (Hoffmann et al, 2014). A few of the Ascl1 + cells in or near the VZ are positive for Olig2 or the OPC-specific marker Pdgfrα, especially in the dorsal spinal cord (Fig.…”

C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

“…However, the key event is the subsequent gradual activation of pluripotency-associated genes (Golipour et al, 2012;Polo et al, 2012). For example, the pluripotency loci (Hoffmann et al, 2014;Mikkelsen et al, 2008;O'Malley et al, 2013;Polo et al, 2012;Shu et al, 2013). Although the molecular mechanisms underlying this observation remain elusive, it is tempting to speculate that reprogramming intermediates transiently pass through a state with increased developmental plasticity that could represent stages of normal development (Orkin and Hochedlinger, 2011).…”